IntroductionIntroduction

Bill Burdett, D.V.M., Intervet Inc.

Bovine Nematode Resistance

An Overview

IntroductionIntroductionToday’s Discussion•Resistance (R) – what is it?•Major nematodes of cattle•Classes of dewormers•Methods of R detection•Characteristics of nematode infection•Fecal sampling•Case histories of R •Using combinations of dewormers

IntroductionIntroductionDefining Resistance

•What R is not: “It is not the development of superworms.” (Anthelmintic Resistance Roundtable, 2005)•Some disagreement as to whether or not it is truly mutation per se•How does it occur? “We are simply creating an environment where that particular genetic makeup survives.” (Dr. Cliff Monahan, OhSU, Anthelmintic Resistance Roundtable, 2005)

IntroductionIntroductionDefining Resistance

•“You are not changing something in the worm. By giving dewormers, we are not inducing resistance – we are simply providing an environment for the resistant parasites to flourish and multiply.” (Dr. Dwight Bowman, Cornell U., Anthelmintic Resistance Roundtable, 2005) •<90% worm egg reduction following use of a specific dewormer = resistance

IntroductionIntroductionScope of the Problem

•Huge in sheep and goats

•Becoming a major issue in cattle, particularly to the endectocides (macrocyclic lactones - avermectins and milbemycins – ivermectin, doramectin, eprinomectin, and moxidectin)

IntroductionIntroductionRisk Factors for Resistance

•Frequent use of same drug class

•Subtherapeutic drug levels from under dosing and/or persistance in the environment at low levels

IntroductionIntroduction

Dru

g Le

vel

Time70 – 80 days

Lethal Dose

EndectocidesFenbendazole

24 hours

Parasite Resistance

CONCEPT ILLUSTRATION

IntroductionIntroductionMajor Cattle Nematodes

•Predominant genera = Ostertagia and Cooperia

•Less predominant genera = Haemonchus, Trichostrongylus, Oesophagostomum, Strongyloides, Trichuris, Nematodirus, and Monezia

IntroductionIntroduction Broad Spectrum Nematode Dewormers

•Group 1 = benzimadazoles (BZ) (attack parasite’s metabolic system)•Group 2 = imidazoles (levamisole, LEV) and hydropyrimidines (pyrantel/morantel) •Group 3 = macrocyclic lactones (avermectins and milbemycins, ML) (attack parasite’s nervous system)

IntroductionIntroductionMethods of Resistance (R) Detection

•Fecal Egg Reduction Count Test (FERCT) for R to any dewormer (only test available for macrocyclic lactones)•Egg hatch test for BZ R•Microagar larval development test for BZ and LEV R

IntroductionIntroductionMethods of Resistance (R) Detection

•PCR based test for BZ R in strongyles of sheep and goats, cattle, and horses•Real time PCR for quantitative determination of gene frequency •Controlled efficacy test – gold standard

IntroductionIntroduction FERCT•Nematode eggs counted on initial fecal exam•Eggs counted again at defined times following treatment, e.g. 14 days•% reduction determined•Only reliable if > 25% of worms resistant

IntroductionIntroduction FERCT•Original product pour on? Confirmation of R using an injectable or oral to eliminate possible problems with malabsorption•Cattle

•Ideal to use animals with minimum count of 100 epg (higher in sheep)•≥17, e.g. 20 cattle per each anthelmintic tested•ML’s

•persistant activity (label) second sample at X days post-treatment depending on species •recommended combined with larval cultures (for appropriate species)

IntroductionIntroduction

Pertinent Things to Remember

And Some Examples of Combination Use and

Resistance

IntroductionIntroduction

Facts

• Calves 3-4 months of age and grazing for at least 2 weeks most susceptible and likely to have most eggs

• Moisture and warm temperatures (>40°F)• Nematodirus – few eggs but very detrimental

to calves

IntroductionIntroduction

Facts

• Small number of animals typically shed most of the eggs, e.g. the 80/20 rule, particularly as animals age

• Recommended minimum number of samples = 20

• Sampling too few animals in a group will likely under represent the small percentage of high egg shedding animals

• Standard deviation exceeds the mean

IntroductionIntroduction

Facts

• Heritability of egg shedding = .3 - .4• Nematodes drive a Th2 immune response

which tends to counter a Th 1 response• Th1 response necessary for good immunity to

intracellular pathogens such as viruses• Single most significant factor of economic loss

from internal parasite infection = appetite suppression

IntroductionIntroduction

Facts

• Physiological responses to GI nematodes• Anorexia• Increased flow rate of feedstuffs through gut• Increases muscle mass in intestinal tract• Decreased fluid absorption

IntroductionIntroduction

Combining FBZ and Avermectin

• First feedyard trial (moderate egg counts,e.g. in the 30’s per gram) demonstrated extra 18 lbs. gain for FBZ + Ivomec pour on versus Ivomec pour on alone (+$20.08)

• Second feedyard trial (low egg counts, 7-9 per gram) showed extra 20 lbs. FBZ + Ivomec pour on versus Dectomax injectable alone ($9.31)

IntroductionIntroduction

Combining FBZ and Avermectin

• Third feedyard trial (moderate egg counts, 150’s per 3 grams) demonstrated reduced egg counts favoring FBZ or FBZ + Ivermectin injectable versus Ivermectin injectable but no difference in economic return

• Dr. Tom Elam economic evaluation of the three trials showed an advantage of using both FBZ and an avermectin of $22.19, $9.01, and $4.20, respectively